Methods Used to Study Placental Function

Direct measurement of placental nutrient transport function in human pregnancy is practically and ethically extremely difficult to achieve. All of the available techniques have drawbacks and involve a trade-off between physiological relevance and the quality of the information derived. There is a very small number of reports of studies where stable isotope-labeled amino acids and fatty acids have been administered to the mother and their appearance measured in the cord blood. These studies have the potential to provide information on dynamic pla-cental nutrient transfer rates in vivo but their interpretation is severely constrained by the number of sequential cord blood samples that can be taken, and the conclusions have therefore been necessarily tentative. Placental function is often inferred by measurements of concentration differences in the maternal and fetal circulations. The most sophisticated of these involve measurements of arterio-venous differences across the umbilical cord at Caesarean section before the cord is cut but such studies are therefore only carried out in very late gestation. Cord blood levels may also be measured following delivery or, more informatively, at earlier stages of development using the invasive method of cordocentesis. However, an important disadvantage of any 'snapshot' of cord blood nutrient concentrations is that these are the net result of both placental delivery and fetal utilization.

Because of the problems with interpretation of results from in vivo studies a number of in vitro approaches have been developed. These include the dually perfused placenta, which retains the cellular structure and metabolic activity of the syncytiotro-phoblast and the placental vascular structure but allows the nutrient composition of the maternal and fetal circulation to be controlled and transfer rates to be measured dynamically using isotopic tracers. The problems with this ex vivo technique are that the placenta tends to be very mature, the efficiency of perfusion cannot be assumed to exactly mimic the in vivo situation, and the composition of the maternal and fetal perfusates are not truly physiological. More detailed but less physiologically relevant to absolute rates of transfer are vesicles formed from the syncytiotrophoblast, which are particularly well suited to the study of nutrient transport mechanisms under highly controlled conditions. The most reductionist methodology involved the identification and characterization of individual transport proteins.

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